This study is a collaboration between NYP-Columbia and NYP-Cornell that seeks to evaluate the use of topical vancomycin and its reduction on surgical site infection (SSI) in craniotomy procedures. Adult patients undergoing craniotomy at either institution will be eligible for participation in this randomized control trial. Patients randomized to the treatment group will receive 3mg of vancomycin powder, mixed with normal saline to make a paste, and applied to the bone craniotomy edges then to the skin edges prior to closure. Subjects in the control group will receive the current standard of care without topical vancomycin. All subjects will undergo swabbing of the anterior nares and the surgical site prior to surgery, once 10-14 days following the operation and 90 days following the operation. The primary outcome measure will be surgical site infection, assessed daily throughout the hospital stay, at the first follow-up visit, and by telephone at 30 days. Secondary outcomes will include length of hospital stay, length of intensive care stay, rate of reoperation and patient mortality. n addition, systemic vancomycin levels will be assessed at 6 hours and 24 hours postoperatively in each patient. Patients who have an external ventricular drain in place will have vancomycin levels assessed daily. In patients who have cranial drains placed, vancomycin concentrations will be analyzed from daily in wound drainage. Skin and nasal flora will be analyzed to assess the impact of topical vancomycin on the patient microbiome. Surgical site infections (SSIs) occur in up to 5% of craniotomy procedures, and are characterized by high morbidity and mortality, increased need for reoperation, longer hospital length of stay and increased healthcare costs. Although there has been a decrease in the incidence of infections following craniotomy secondary to prophylactic intravenous antibiotics, proper sterile techniques, and other interventions, SSIs continue to significantly impact morbidity, mortality, and cost burden. Although never studied in craniotomy procedures, the application of topical vancomycin to the surgical site prior to wound closure has demonstrated a reduction in SSIs in spine, cardiac and ophthalmologic procedures. The benefits of using prophylactic vancomycin topically, as opposed to intravenously, include reduced systemic levels of the drug, and therefore, a decreased probability of adverse events related to the drug, such as inducing resistance among native flora. We propose a randomized control trial to evaluate the effectiveness of topical vancomycin in reducing SSIs rates following craniotomy procedures.